The major long range objective of my research is the clarification and elucidation of phenomena involved in successful regenerative repair in the vertebrate central nervous system (CNS). More specifically, on the basis of morphological studies, I am concerned about the basic differences in the response of damaged CNS structures of higher vertebrates that fail to establish severed connections and those of lower vertebrates that are readily restablished, using the optic nerve as an experimental model. In addtion, I am interested in the relationship of humoral agents (Nerve Growth Factor) to CNS regenerative repair. I have already begun some encouraging studies in this area with particular emphasis on glial cell response to optic nerve lesion in the newt. My initial findings have led me to conclude that one of the important determining factors in successful reestablishment of severed CNS connections is found in glial cell reactivity. The proposed program will be a continuation and expansion of my present interests in glial cell response to CNS injury in regenerating visual systems in addition to initiation of pilot studies relating to nerve growth factor effects in optic nerve regeneration. The problem will be approached in the following manner: (1) a continuation and expansion of my present ultrastructural studies dealing with general aspects of newt optic nerve degenerative and regenerative phenomena; (2) an indepth analysis of glial cell phagocytic and regenerative responses in the newt optic nerve and (3) a comparative study of glial cell response in regenerative repair in fish, urodele and anuran visual systems contrasted with that of nonregenerating vertebrates (reptiles and mammals). In the course of these studies, I will be using accepted light microscopy and fine structure techniques as well as associated types of cytochemical assays. It is my hope that this program will begin to demonstrate to us the specific cellular responses (glial and neuronal) to CNS injury responsible for successful, functional regenerative repair. BIBLIOGRAPHIC REFERENCES: Glaze, K.A. and J.E. Turner 1976. The effect of the nerve growth factor antiserum on the regenerating optic nerve of the newt (Triturus viridescens). Anat. Rec., 184: 411. Turner, J.E. and K.A. Glaze 1977. The early stages of Wallerian degeneration in the severed optic nerve of the newt (Triturus viridescens). Anat. Rec., in press.